Currently, in fields such as biology and medicine, in order to study characteristics of biological behaviors related to organisms such as cells, tissue and organs, for example, uptake of organism metabolite such as glucose, amino acids and fatty acids, a detecting scheme is widely adopted. The detecting scheme includes: in-vitro cultivating living biological tissue by adding the above metabolites with a radioactive nuclide label into a biochemical cultivating instrument; and detecting radioactivity distribution information of a sample by a radiation detector, to reflect the number of labels taken by the sample. Compared with another conventional scheme for detecting an in-vitro tissue physiological activity based on fluorescence imaging, the above scheme has the following advantages: since imaging methods such as PET and SPECT which use a same label and a same monitoring means may be adopted in clinic, a conclusion obtained with an in-vitro experiment can be used to guide an in-vivo experiment better, and the in-vitro experiment and the in-vivo experiment can be cross-checked with each other.
For example, in one of important methods for oncology research, different medicines are added into a tumor cell strain cultivated in-vitro, and an impact on a biochemical activity by the medicines is observed to evaluate the curative effect of the medicines. A rate at which a tumor cell makes an uptake of metabolite, especially glucose, is closely related to a biological activity of the tumor cell, which is represented as related to sensitivity on medicine of the tumor in dine. For researching a physiological mechanism of the tumor and evaluating a medicine, it is critical to monitor, based on the in-vitro experiment and the in-vivo experiment, a process in which a tumor cell makes an uptake of glucose. For a same administration individual, the biochemical activity in a level of cell and tissue is researched by in-vitro cultivating and monitoring the tissue of a body, and a biological research in a level of organ and organism is completed with an in-vivo imaging, thereby achieving a multilevel evaluation of medicine effect under a same receptor source, a same monitoring means and a same evaluation system, and realizing an individual medical treatment truly.
In one of the current methods for quantitatively monitoring an in-vitro metabolism process includes: after multiple batches of same tumor cell strains are cultivated in a cultivating dish and the glucose with the radioactive nuclide label or the like, such as 18F-FluoroDeoxyGlucose (18F-FDG) solution, is added into the cultivating dish, the tumor cell strains are incubated in a cell incubator box. Then, cells of different batches are collected at several time points, cultivating solution is cleaned and the collected cells are placed in a fully enclosed gamma counter to monitor left radiation doses in the respective cells, thereby calculating the amount of the glucose taken by the tumor cell strain at different time points[1][2].
In the above scheme with the static cultivating device and the fully enclosed gamma counter, substantially, multiple sampling points in time are obtained by increasing the number of the same disposable samples. An apparent disadvantage of the above scheme is that, only information of metabolite cumulative doses at several discrete time points can be obtained and it is difficult to measure an uptake rate of the tissue dynamically and continuously, hence the obtained information can not reflect a full view of a biochemical process. Since only one sample can be monitored in the fully enclosed gamma counter once and the cultivating solution needs to be cleaned to leave only adherent cells before the sample is monitored, the sample can not be reused after the sample is monitored. In this case, a large number of samples need to be incubated to obtain more accurate activity-time information, and in a monitoring, it is required to try to operate a same batch of samples simultaneously to ensure a conform sample test condition. In short, if the above scheme is adopted to perform a continuous monitoring, an experiment cost and an operation complexity are unbearable, a radiation harm suffered by an operator is increased hundredfold as compared with a single experiment, and an error is more easily caused by manual operations in multiple times and differences between samples of different batches.
In another scheme for quantitatively monitoring the in-vitro metabolism process, a detecting is performed with a Positron Emission Tomography (Positron Emission Tomography, hereinafter referred to as PET) imager [1]. The PET instrument may rebuild an image reflecting a distribution of radioactivity in an imaging region by detecting position information of a couple of gamma photons generated in a positron decay of radioactive nuclide. A cultivating dish containing radioactive metabolites is placed in a PET detector ring and is imaged. Since a light and a shade in a PET image represent different radioactivity, activity information may be obtained by calculating a sum of pixel values inside a cultivating well.
In the scheme using the PET, a sensitivity issue needs to be addressed firstly. An imaged object of the PET instrument is a human body or an animal, hence a structure of a detector of the PET instrument is annular and a ring gauge is generally tens of centimeters. In this case, a detecting angle is small for a cultivating dish with a flat-plate structure, and a detecting sensitivity is low. In addition, the PET instrument is used to performing an imaging, the number of cells cultivated in-vitro is small (105˜106 per cultivating well) and the number of injected radioactive labels is small (10˜104 Bq). In this case, it is difficult to achieve a real-time monitoring due to a prolonged imaging time for acquiring sufficient imaging data and a time consumption for image rebuilding and processing. Since a spatial resolution of the PET instrument is generally several millimeters, a capability for distinguishing radioactive events from different cultivating wells is limited. Finally, since a capacity of the PET instrument is large and it is expensive to buy and maintain the PET instrument, the PET instrument is not suitable to serve as an analysis tool for in-vitro metabolism level research.
In another common method for quantitatively monitoring the in-vitro metabolism process, a gamma camera is adopted [2]. A basic structure of the gamma camera is the same as that of a single PET detecting module, but a collimator needs to be mounted in front of a scintillation crystal, to prevent a gamma ray in a non-specified range and a non-specified direction from entering the crystal, hence information is acquired orientedly. When being used, the gamma camera is placed directly above a detected object. Gamma rays filtered by the collimator are detected through the scintillation crystal, a photoelectric conversion component and a backend electronics, and position information of the gamma rays is calculated. After the data is acquired, a two-dimension projection image representing a radioactivity distribution of the detected object may be obtained based on a distribution of incident positions of the gamma rays.
In the scheme using the gamma camera, a sensitivity issue still needs to be addressed. Since the collimator is needed in the gamma camera, the detector can not be against the detected object. In this case, a detecting angle is small and a sensitivity is small (about 1% for a single cultivating well), and it takes a long acquisition time to acquire one frame of image. Therefore, it is difficult to achieve a real-time monitoring. In addition, an existence of the collimator and a calculation of position information degrade the spatial resolution of the detector [3][4]. In this case, a source of gamma photon can not be calculated accurately, and errors may exist in the final-obtained radioactivity count for cultivating positions.
Furthermore, experiment designs in cell and molecule levels tend to be high-throughput, that is, large numbers of samples are monitored in one experiment. Therefore, a multichannel cultivating instrument such as a multiwell cell cultivating plate is generally adopted. The multiwell cell cultivating plate is formed by arranging multiple cultivating dishes with a same specification on a same plate in array, and is widely used as a cultivating instrument in a biochemical field due to its high integration level, standardization and operational convenience. However, in the above three detecting methods, the fully enclosed gamma counter can only monitor one sample once, and can not monitor multiple cultivating dishes distinguishingly. The PET and the gamma camera can not distinguish counts for adjacent regions in two cultivating channels accurately, have different detecting sensitivities for different cultivating channels, and thus are not suitable to serve as a monitoring apparatus in a high-throughput experiment.
Therefore, for the above technical issues, a new multichannel in-vitro metabolism real-time monitoring apparatus needs to be provided to overcome the above defects.    [1] Fischer B M, Olsen M W B, Ley C D, et al. How few cancer cells can be detected by positron emission tomography? A frequent question addressed by an in vitro study[J]. European journal of nuclear medicine and molecular imaging, 2006, 33(6): 697-702.    [2] Zinn K R, Chaudhuri T R, Buchsbaum D J, et al. Detection and measurement of in vitro gene transfer by gamma camera imaging[J]. Gene therapy, 2001, 8(4): 291-299.    [3] Scopinaro F, Pani R, De Vincentis et al. High-resolution scintimammography improves the accuracy of technetium-99m methoxyisobutylisonitrile scintimammography: use of a new dedicated gamma camera[J]. European journal of nuclear medicine, 1999, 26(10): 1279-1288.    [4] Xiaohua Li, Ruzhen Gao, Fuxiang Liu. Influence of detect distance on space resolution of γ camera system[J]. Chinese Medical Equipment Journal, 1990, 03: 6-8.